CRAPT-M: An effective prognostic predictor for hepatocellular carcinoma patients treated with locoregional-bevacizumab-immunotherapy

Table 1 The risk factors and corresponding scores

Risk factors	Score
CRP (mg/dL)
< 1.0	0
≥ 1.0	7
ALB (g/L)
< 35	0
≥ 35	5
PIVKA-II (mAU/mL)
< 1500	0
≥ 1500	5
TBIL (mg/dL)
< 1.0	0
≥ 1.0	4
MVI
No	0
Yes	4

CRP: C-reactive protein; ALB: Albumin; PIVKA-II: Protein induced by vitamin K absence or antagonist-II; TBIL: Total bilirubin; MVI: Macrovascular invasion.

Table 2 The definitions of CRAPT-M and Simple-CRAPT-M

	CRAPT-M group (total score)	Simple-CRAPT-M group (clinical risk factors count)
Low-risk	≤ 4	0-2 clinical risk factors (total score ≤ 12)
Intermediate-risk	5-12	-
High-risk	≥ 13	3-5 clinical risk factors (total score ≥ 13)

Table 3 Baseline characteristics of hepatocellular carcinoma patients receiving locoregional-bevacizumab-immunotherapy, n (%)

Variables	Total (n = 443)	CRAPT-M-low risk (n = 58)	CRAPT-M-intermediate risk (n = 162)	CRAPT-M-high risk (n = 223)	P value
Sex					0.013
Male	396 (89.4)	47 (81.0)	141 (87.0)	208 (93.3)
Female	47 (10.6)	11 (19.0)	21 (13.0)	15 (6.7)
Age (year)					0.496
≥ 65	68 (15.3)	11 (19.0)	21 (13.0)	36 (16.1)
< 65	375 (94.7)	47 (81.0)	141 (87.0)	187 (83.9)
HBV					0.076
Yes	406 (91.6)	49 (84.5)	148 (91.4)	209 (93.7)
No	37 (8.4)	9 (15.5)	14 (8.6)	14 (6.3)
Tumor size (cm)					< 0.001
≥ 7.0	311 (70.2)	24 (41.4)	110 (67.9)	177 (79.4)
< 7.0	132 (29.8)	34 (58.6)	52 (32.1)	46 (20.6)
Tumor number					0.465
Single	137 (30.1)	19 (32.8)	55 (34.0)	63 (28.3)
Multiple	306 (69.1)	39 (67.2)	107 (66.0)	160 (71.7)
Extrahepatic metastasis					< 0.001
Yes	165 (37.2)	17 (29.3)	43 (26.5)	105 (47.1)
No	278 (62.8)	41 (70.7)	119 (73.5)	118 (52.9)
BCLC stage					< 0.001
A	34 (7.7)	10 (17.2)	22 (13.6)	2 (0.9)
B	95 (21.4)	12 (20.7)	57 (35.2)	26 (11.7)
C	314 (70.9)	36 (62.1)	83 (51.2)	195 (87.4)
Child-Pugh					< 0.001
A	384 (86.7)	58 (100.0)	155 (95.7)	171 (76.7)
B	59 (13.3)	0 (0.0)	7 (4.3)	52 (23.3)
Systemic therapies					0.901
Atezolizumab + bevacizumab	194 (43.8)	27 (46.6)	70 (43.2)	97 (43.5)
Sintilimab + bevacizumab	249 (56.2)	31 (53.4)	92 (56.8)	126 (56.5)
Transarterial therapies					0.196
HAIC	378 (85.3)	45 (77.6)	141 (87.0)	192 (86.1)
TACE	65 (14.7)	13 (22.4)	21 (13.0)	31 (13.9)
PLTs	200.7 ± 97.7	189.1 ± 91.6	213.0 ± 101.3	194.8 ± 96.1	0.124
WBC	7.6 ± 3.2	6.8 ± 3.4	7.6 ± 3.0	7.8 ± 3.3	0.08

HBV: Hepatitis B virus; BCLC: Barcelona Clinic Liver Cancer; HAIC: Hepatic arterial infusion chemotherapy; TACE: Transarterial chemoembolization; PLT: Platelet; WBC: White blood cell.

Table 4 Treatments efficacy, n (%)

Variables	Overall (n = 443)	CRAPT-M-low-/intermediate-risk (n = 220)	CRAPT-M-high-risk (n = 223)	P value
RECIST				0.059
CR	2 (0.5)	0 (0.0)	2 (0.9)
PR	155 (35.0)	83 (37.7)	72 (32.3)
SD	223 (50.3)	114 (51.8)	109 (48.9)
PD	63 (14.2)	23 (10.5)	40 (17.9)
mRECIST				0.08
CR	21 (4.7)	12 (5.5)	9 (4.0)
PR	236 (53.3)	127 (57.7)	109 (48.9)
SD	123 (27.8)	58 (26.4)	65 (29.1)
PD	63 (14.2)	23 (10.5)	40 (17.9)
ORR	157 (35.4)	83 (37.7)	74 (33.2)	0.368
mORR	257 (58.0)	139 (63.2)	118 (52.9)	0.036
DCR	380 (85.8)	197 (89.5)	183 (82.1)	0.034

RECIST: Response Evaluation Criteria in Solid Tumors; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; mRECIST: Modified Response Evaluation Criteria in Solid Tumors; ORR: Objective response rate; mORR: Modified objective response rate; DCR: Disease control rate.

Table 5 Multivariate Cox regression analyses of the prognostic factors for overall survival and progression-free survival

Variable	Multivariate Cox regression of OS			Multivariate Cox regression of PFS
	HR	95%CI	P value	HR	95%CI	P value
Tumor size (cm)
0-7
> 7	1.10	0.79-1.53	0.59
Tumor number
Solitary
Multiple	1.59	1.15-2.21	< 0.01	1.41	1.05-1.89	0.02
Child-Pugh
A
B	1.31	0.92-1.88	0.14	1.20	0.86-1.66	0.29
BCLC
A
B				0.98	0.56-1.76	0.94
C				0.99	0.94-1.76	0.98
CRAFITY
0
1	1.03	0.58-1.85	0.92	0.79	0.50-1.25	0.32
2	1.09	0.56-2.15	0.79	0.85	0.49-1.47	0.56
CRAPT-M
Low-risk
Intermediate-risk	1.50	0.82-2.73	0.19	1.10	0.69-1.76	0.68
High-risk	2.52	1.34-4.75	< 0.01	1.87	1.13-3.09	0.01
Extrahepatic metastasis
No
Yes	1.75	1.28-2.41	< 0.01
Transarterial therapies
HAIC
TACE				1.28	0.94-1.76	0.12

OS: Overall survival; PFS: Progression-free survival; BCLC: Barcelona Clinic Liver Cancer; HAIC: Hepatic arterial infusion chemotherapy; TACE: Transarterial chemoembolization.